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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04372433
Other study ID # IO-202-CL-001
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 14, 2020
Est. completion date January 31, 2027

Study information

Verified date March 2024
Source Immune-Onc Therapeutics
Contact Yasuhiro Tabata, MD, PhD
Phone 650-457-1741
Email yasuhiro.tabata@immuneonc.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with AML with monocytic differentiation and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D)


Description:

This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients with Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients


Recruitment information / eligibility

Status Recruiting
Enrollment 106
Est. completion date January 31, 2027
Est. primary completion date January 31, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Patients must be =18. 2. For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following: 1. Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic differentiation according to the World Health Organization 2016 criteria and has failed treatment with available therapies known to be active for AML. 2. Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML 3. Part 2 Expansion Phase: 1. Relapsed or refractory LILRB4high AML with myelomonocytic or monoblastic/monocytic differentiation and has failed treatment with available therapies known to be active for AML. 2. Hypomethylating-agent naive CMML regardless of LILRB4 expression levels. 3. Newly diagnosed high LILRB4 expression monocytic AML patients considered to be ineligible for standard induction therapy. 4. Patients must be amenable to serial BM aspirates/biopsies and peripheral blood sampling during the study. 5. Patients must be able to understand and willing to sign an informed consent. A legally authorized representative may consent. 6. Patients must have an ECOG performance status of 0 to 2 7. Patients must have adequate hepatic function 8. Patients must have adequate renal function 9. Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. 10. Patients must be off systemic calcineurin inhibitors for at least 4 weeks prior to study drug treatment. 11. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Exclusion Criteria: 1. Patients who have previously received a monoclonal antibody therapy targeting LILRB4. 2. Patients who have undergone HSCT within 60 days of the first dose of IO-202. 3. Patients who received systemic anti-cancer therapy or radiotherapy <7 days prior to their first day of study drug administration (Hydroxyurea or leukapheresis is allowed up to 24 hours prior to the first dose. 4. Patients who received an investigational agent <7 days prior to their first day of study drug administration. 5. Patients for whom potentially curative anti-cancer therapy is available. 6. Patients who are pregnant or breastfeeding. 7. Patients with uncontrolled, active infection. 8. Patients with known hypersensitivity to any of the components of the IO-202 formulation. 9. Patients with known pulmonary lesions and/or history of pneumonitis or interstitial lung disease. 10. Active known malignancy. 11. Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40%. 12. Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade =2. 13. Known or suspected hypersensitivity to recombinant proteins. 14. Known active bacterial, viral, and/or fungal infection. 15. Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol. 16. Patients with clinical signs and/or symptoms suggesting active, uncontrolled central nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia. 17. Patients with immediately life-threatening, severe complications of leukemia. 18. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration. 19. Current active treatment in another interventional therapeutic clinical study. 20. Chronic systemic corticosteroid treatment with a dose of >10 mg prednisone/day or dose equivalent. 21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study. 22. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis. 23. Hyperleukocytosis (leukocytes =25 x 10e9/L) at first dose of IO-202.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
IO-202
IO-202 as monotherapy
IO-202 and Azacitidine
IO-202 and azacitidine combination therapy
IO-202 and Azacitidine + Venetoclax
IO-202 and azacitidine + venetoclax combination therapy
IO-202 and Azacitidine
IO-202 and azacitidine combination therapy

Locations

Country Name City State
United States Winship Cancer Institute of Emory University (105) Atlanta Georgia
United States University of Colorado, Anschutz Medical Campus (103) Aurora Colorado
United States The University of Chicago (113) Chicago Illinois
United States Cleveland Clinic, Taussig Cancer Institute (111) Cleveland Ohio
United States University of Texas Southwestern, Simmons Comprehensive Cancer Center (104) Dallas Texas
United States University California, Davis (117) Davis California
United States City of Hope (106) Duarte California
United States MD Anderson Cancer Center (101) Houston Texas
United States University of California, Irvine (107) Irvine California
United States UCLA, Medical Center Division of Hematology/Oncology (119) Los Angeles California
United States Weill Cornell Medical College, New York Presbyterian Hospital (110) New York New York
United States Stanford University (114) Palo Alto California
United States Oregon Health and Science University, Center for Hematologic Malignancies (116) Portland Oregon
United States University of California, San Francisco (118) San Francisco California

Sponsors (2)

Lead Sponsor Collaborator
Immune-Onc Therapeutics California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other To correlate target expression with response rates Statistical correlation levels of target expression on leukemic blasts with response rate Through study completion, an average of 1 year
Other To correlate target expression with rates of adverse events Statistical correlation of target expression on leukemic blasts with adverse event rates Through study completion, an average of 1 year
Other To evaluate immunophenotype of leukemic blasts after study treatment. Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment Through study completion, an average of 1 year
Primary Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events. Incidence of adverse events From first dose of IO-202 to 30 days following last study treatment
Primary Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events. Severity of adverse events From first dose of IO-202 to 30 days following last study treatment
Primary Tolerability of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence and duration of dose interruptions and dose reductions of study treatment. Incidence dose interruptions and dose reductions From first dose of IO-202 to 30 days following last study treatment
Secondary To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax) Maximum concentration (Cmax) of IO-202 Through study completion, an average of 1 year
Secondary To characterize the PK of IO-202 and IO-202 IO-202 plus azacitidine ± venetoclax as defined by area under the curve (AUC) measure area under the curve (AUC) of IO-202 Through study completion, an average of 1 year
Secondary To evaluate the incidence of anti-drug antibodies against IO-202 Measure anti-drug antibodies in plasma. Through study completion, an average of 1 year
Secondary To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax Measure response rates in patients with anti-drug antibodies. Through study completion, an average of 1 year
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